Actimab-A Trials with Keytruda or Opdivo

Keytruda developed and commercialized by Merck & Co. and Opdivo developed and commercialized by Bristol Myers Squibb, collectively generated $38.8 billion in sales in 2024 across several solid tumor cancer indications. However, the efficacy of these drugs has shown to be limited by a certain type of cell known as MDSCs or Myeloid Derived Suppressor Cells which accumulate in the tumor microenvironment. MDSCs express the CD33 antigen which is targeted by Actimab-A.  The rationale for studying Actimab-A in combination with either Keytruda  or Opdivo is based on the premise that depleting MDSCs with Actimab-A will improve the efficacy of these drugs.

MDSCs are immune-suppressive cells that help tumors evade immune detection and promote disease progression. They are overexpressed in the tumor microenvironment in several different solid tumors and associated with poor outcomes. They work by multiple mechanisms but most relevant to PD-1 inhibitors which work by keeping T-cells active is that MDSCs prevent T-cells from recognizing and attacking cancer cells. There is considerable preclinical scientific evidence in the literature that depleting MDSCs could be a viable strategy in improving the outcomes of PD-1 directed immunotherapy, however, there have been no viable clinical approaches that have been tried successfully to our knowledge.  MDSCs are known to express the CD33 antigen which is the target of Actimab-A.  Actinium has also generated published and unpublished preclinical data showing that Actimab-A can selectively deplete MDSCs in solid tumors.  Actinium believes that in the clinic Actimab-A can deplete CD33 expressing MDSCs and hence improve the outcomes with PD-1 inhibitors such as Keytruda and Opdivo..

The Actimab-A solid tumor program is comprised of several controlled, head-to-head clinical trials that will evaluate the combination of Actimab-A with Keytruda versusKeytruda alone, and Actimab-A with Opdivo versus Opdivo  alone. The initial tumors that are being targeted are HNSCC or Head and Neck Squamous Cell Carcinoma and NSCLC or Non-Small Cell Lung Cancer with a separate trial for each indication. The patient population for these trials will be adults with PD-L1 expression and locally advanced metastatic HNSCC or NSCLC randomized to either Actimab-A alone or Actimab-A with a specific checkpoint inhibitor. The objective of each trial would be to evaluate the safety and tolerability as well as following endpoints including ORR – Overall Response Rate, PFS – Progression Free Survival and OS – Overall Survival. Further, the following biomarker data would be collected including the pattern of depletion of CD33+ MDSCs and T-Cell activity in peripheral blood. Actinium expects to present initial proof of concept clinical data from the first of these trials in the second half of 2025 as well as provide an update on the outlook for the rest of the trials in the Actimab-A solid tumor program.